The present invention relates to methods and devices for treating aneurysms. More particularly, the invention relates to methods and devices for treating abdominal aortic aneurysms by delivering one or more therapeutic agents at or near the aneurysm.
An aneurysm is a sac formed by localized dilatation of the wall of an artery, a vein, or the heart. Common areas where aneurysms occur and cause potential medical conditions include the coronary arteries, the carotid arteries, various cerebral arteries, and the abdominal aorta. When a local dilatation of a vessel occurs, irregular blood flow patterns result, typically leading to clot formation. Typically, the wall of the vessel also progressively dilates and weakens, often resulting in vessel rupture. Vessel rupture, in turn, often causes dramatic negative health consequences such as a stroke, when a cerebral vessel ruptures, or even death, when an abdominal aortic aneurysm (“AAA”) ruptures. In light of these consequences, improved treatment methods and devices for aneurysms are constantly being sought. Although the following discussion focuses on AAA treatment, it is equally applicable to aneurysms in other locations.
Researchers have hypothesized that the development, expansion and rupture of AAAs are all related to connective tissue destruction. For a discussion of this hypothesis, see for example, “Pharmacologic suppression of experimental abdominal aortic aneurysms: A comparison of doxycycline and four chemically modified tetracyclines,” Curci, John A., Petrinec, Drazen, et al., Journal of Vascular Surgery, December 1998, vol. 28, no. 6, 1082-1093 (hereinafter “Curci article”), the contents of which are hereby incorporated by reference. Connective tissue destruction, in turn, has been linked to the presence of a number of enzymes which break down blood vessel wall connective tissues such as elastin. Examples of such “elastolytic” enzymes include serine proteinases such as metalloproteinases (“MMPs”). It has been found that increased levels of MMPs and other elastolytic enzymes are typically present in AAAs.
Researchers have also found that AAAs and other aneurysmal vessels often contain elevated levels of the Chlamydia pneumoniae bacterium, which may be another cause of aneurysmal disease. Thus, AAA treatments focussing on drug therapy to combat MMPs and similar enzymes, to combat C pneumoniae, to generally suppress collagen destruction, and/or to increase collagen production are currently being developed. For discussions of investigations into such treatments, see for example the Curci article; “Are There Ways to Retard the Growth of Abdominal Aortic Aneurysms?” White, John V., 2001 Clinical Congress PG 10, Session IIA: New Approaches to Old Problems: Vascular Disease, 30-33 (hereinafter “White article”); “Indicators of infection with Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysms,” Lindholt, Jes S., Ashton, Hillary A., et al., Journal of Vascular Surgery, August 2001, vol. 34, no. 2, 212-215 (hereinafter “Lindholt/Ashton article”); “Randomized double-blind controlled trial of roxithromycin for prevention of abdominal aortic aneurysm expansion,” Vammen, S., Lindholt, J. S., et al., British Journal of Surgery 2001, 88, 1066-1072 (hereinafter “Vammen article”); “Treatment of Chlamydia pneumoniae infection with roxithromycin and effect on neointima proliferation after coronary stent placement (ISAR-3): a randomized, double-blind, placebo-controlled trial,” Neumann, Franz-Josef, Kasrati, Adnan, et al. The Lancet, Jun. 30, 2001, vol. 357, 2085-2089 (hereinafter “Neumann article”); “Five-year Results of Elastin and Collagen Markers as Predictive Tools in the Management of Small Abdominal Aortic Aneurysms,” Lindholt, J. S., Heickendorff, L., et al., Eur J Vasc Endovasc Surg, March 2001, vol. 21, 235-240 (hereinafter “Lindholt/Heikendorff article”); and “Antibodies Against Chlamydia pneumoniae Predict the Need for Elective Surgical Intervention on Small Abdominal Aortic Aneurysms,” Vammen, S., Lindholt, J. S., et al., Eur J Vasc Endovasc Surg, August 2001, vol. 22, 165-168 (hereinafter “Vammen/Lindholt article”); the contents of all of the foregoing articles being hereby incorporated by reference.
As discussed in many of the above-referenced articles, scientists continue to research treatment of AAAs by administration of one or more systemic therapeutic agents. Some agents which have been tried include doxycycline, tetracycline, tetracycline derivatives, roxithromycin and propranolol. Such systemic treatments have shown significant levels of success, typically in vitro or in laboratory rats. Administration of agents on a systemic level, however, such as by oral or intravenous administration, has certain inherent drawbacks. The most obvious drawback to any medication is the unwanted side effects that accompany the drug. When a drug is given systemically to treat a localized medical condition, the dose of the drug is typically larger than would be ideal and, thus, has a greater likelihood of causing unwanted or harmful side effects. On the other hand, if a therapeutic drug used to treat a local condition is delivered locally at or near the treatment site, doses can usually be decreased to more tolerable levels.
In the pharmaceutical treatment of AAAs with antibiotics, antibiotic derivatives, propranolol and/or other agents, researchers have already found that beneficial effects appear to be dose dependent. (See, for example, the Curci article.) If sufficient doses of medications to treat AAAs are administered systemically, the medications are likely to have unwanted side effects. Listed side effects for doxycycline, for example, include anorexia, nausea, vomiting, diarrhea, rashes, kidney toxicity, and anemia. At the very least, antibiotic treatment may lead to unwanted antibiotic resistance, already a growing problem in the United States. Propranolol, which is commonly used to treat high blood pressure but has been found to have beneficial effects on AAAs, can cause slowed heart rate, lightheadedness, abnormally low blood pressure, depression, nausea, vomiting, abdominal cramping, bronchospasm, agranulocytosis, and/or various other adverse effects in some people. Therefore, it would be advantageous to have methods and devices for delivering one or more therapeutic agents to a treatment area at or near a AAA. Such delivery may enhance medical therapy of AAAs while limiting adverse drug reactions in treated patients.